Project description:Few families of signaling factors have been implicated in the control of development. Here we identify the neuropeptides nociceptin and somatostatin, a neurotransmitter and neuroendocrine hormone, as a class of developmental signals in chick and zebrafish. We show that signals from the anterior mesendoderm are required for the formation of anterior placode progenitors with one of the signals being somatostatin. Somatostatin controls ectodermal expression of nociceptin and both peptides regulate Pax6 in lens and olfactory progenitors. Consequently, loss of somatostatin and nociceptin signaling leads to severe reduction of lens formation. Our findings not only uncover these neuropeptides as developmental signals, but also identify a long-sought-after mechanism that initiates Pax6 in placode progenitors and may explain the ancient evolutionary origin of neuropeptides, pre-dating a complex nervous system. We used progenitors for anterior and posterior sensory placodes dissected from chick embryos HH5-7; these were either processed immediately or cultured for 5 hrs to hybridise to Affymetrix chick array. We aimed to identify genes that are co regualted with Pax6, a key regulator of lens and olfactory progenitor cells. Pax6 is normally present in anterior, but not posterior placode precursors, but upregulated in both after 5 hrs culture.
Project description:Few families of signaling factors have been implicated in the control of development. Here we identify the neuropeptides nociceptin and somatostatin, a neurotransmitter and neuroendocrine hormone, as a class of developmental signals in chick and zebrafish. We show that signals from the anterior mesendoderm are required for the formation of anterior placode progenitors with one of the signals being somatostatin. Somatostatin controls ectodermal expression of nociceptin and both peptides regulate Pax6 in lens and olfactory progenitors. Consequently, loss of somatostatin and nociceptin signaling leads to severe reduction of lens formation. Our findings not only uncover these neuropeptides as developmental signals, but also identify a long-sought-after mechanism that initiates Pax6 in placode progenitors and may explain the ancient evolutionary origin of neuropeptides, pre-dating a complex nervous system.
Project description:We compared the effects of nociceptive neuropeptides and nociceptors on DCs by means of coculture of Flt3L-induced bone marrow-derived DCs and primary mouse nociceptors.
Project description:Very little is known about the genetic modulation of nictation, a host-finding strategy used by infective juveniles of many pathogenic nematodes, as well as a phoretic strategy of Caenorhabditis elegans dauers. We here use a mass spectrometry-driven approach to find neuropeptides involved in the modulation of this behavior. We identified 126 neuropeptides in infective juveniles of the commercially relevant entomopathogenic nematode Steinernema carpocapsae, 75 of which have orthologs in the model organism C. elegans. To prioritize candidates for causality testing in light of the stage-restricted nictation behavior, we developed quantitative peptidomic assays and carried out targeted proteomic measurements that allows comparing neuropeptide levels at different C. elegans life stages. Our results show that virtually all 164 quantified neuropeptides are more abundant in dauers compared to L3 juveniles. Even so, not all are relevant to nictation, and we identify the neuropeptide genes flp-7 and flp-11 as novel regulators of nictation.
Project description:The goal of this project was to identify potential neuropeptides in extracts from larvae of the nemertean species Lineus longissimus.
Project description:It has been well established that parvulbumin (PV) interneurons in the adult dentate gyrus (DG) regulate radial-glia like neural stem cells (rNSCs) through tonic GABA signaling. However, several major local interneuron subtypes co-release GABA and neuropeptides. Virtually nothing is known about whether and how endogenous neuropeptides regulate rNSCs. Here we demonstrate an unprecedented role of endogenous CCK in regulating rNSCs and hippocampal neurogenesis through distinctive states of the local astrocytes. Specifically, stimulating CCK release leads to increased Ca2+ transients in local astrocytes, and the subsequent astrocytic glutamate release promotes rNSC proliferation and neurogenesis via glutamate receptor mediated MAPK/ERK signaling cascade. In contrast, suppression of CCK synthesis switches resident astrocytes to a reactive state, which leads to decreased proliferation of rNSCs by regulating a gene network that negatively regulates rNSC proliferation. These findings have broad implications in multiple neuropathological conditions associated with altered CCK level, neuroinflammation, and impaired hippocampal neurogenesis.
Project description:Neuropeptides are a class of endogenous peptides that have key regulatory roles in biochemical, physiological, and behavioral processes. Mass spectrometry analyses of neuropeptides often rely on protein informatics tools for database searching and peptide identification. As neuropeptide databases are typically experimentally built and comprised of short sequences with high sequence similarity to each other, we developed a novel database searching tool, HyPep, which utilizes sequence homology searching for peptide identification. HyPep aligns database-free, de novo sequenced peptide sequences generated through PEAKS software with neuropeptide database sequences to identify neuropeptides based on an alignment score. HyPep performance was optimized using LC-MS/MS measurements of peptide extracts from various C. sapidus neuronal tissue types and compared with a commercial database searching software, PEAKS DB. HyPep identified more neuropeptides from each tissue type than PEAKS DB at 1% false discovery rate and the false match rate from both programs was 2%. In addition to identification, this report describes how HyPep can aid in the discovery of novel neuropeptides.
Project description:Ethologists predicted that parental care evolves by modifying suitable behavioural precursors in the asocial ancestor. Traits such as nest building, defensive and aggressive behaviours, and potentially shared resources evolve to offspring protection and defence, and feeding. From this ethological principle, we further predicted that the evolved mechanistic changes would reside in genetic pathways underlying these behavioural precursors. While gene expression is difficult to detect for some molecules like neuropeptides, we tested our hypothesis by measuring abundance of neuropeptides in different behavioural states using LC-MS in female burying beetles, Nicrophorus vespilloides. Parenting in this species is extensive and complex as caring adults regurgitate food to begging, dependent offspring. We identified neuropeptides by sampling peptide abundance in female brains collected from three different behavioural states: solitary virgins, actively parenting, or post-parenting solitary adults. We identified 133 peptides belonging to 18 neuropeptides. Of these 18, eight differed in abundance in one or more state. We found increased abundance during parenting in seven of the eight. None of the identified neuropeptides have previously been associated with parental care, but all have known roles in predicted behavioural precursors of mating, resource defence, feeding, or social tolerance. Two, tachykinin and sulfakinin, influence multiple pathways. Our study supports the prediction that appropriate behavioural precursors are likely targets of selection during the evolution of parenting. Evolutionary principles predicted neuropeptides influencing social behaviour, and our results provide several new candidate neuropeptides underpinning parenting.
Project description:Post-traumatic stress disorder (PTSD) is a psychiatric disorder that affects the health of a wide range of the population. However, its underlying neurophysiological mechanisms remain unclear due to the limited understanding of neuronal signaling molecules such as neuropeptides. Here, we developed mass spectrometry (MS) based qualitative and quantitative analysis to profile the neuropeptides in the control and predator odor exposure rat PTSD model group. In total, 628 unique neuropeptides can be identified across 5 fear circuitry-related brain regions. Meanwhile, brain region-specific changes of serval neuropeptide families including granin, ProSAAS, opioid peptide, cholecystokinin, and tachykinin can be observed in the PTSD group. Neuropeptides from the same protein precursor were also found to vary in different brain regions. This study reveals for the first time the interaction between neuropeptides and severe stress, providing insights into the molecular mechanism of PTSD and corresponding therapeutic strategy.